Spath Sabine, Roan Florence, Presnell Scott R, Höllbacher Barbara, Ziegler Steven F
Center for Fundamental Immunology, Benaroya Research Institute, Seattle, WA 98101, USA.
Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, WA 98109, USA.
iScience. 2022 Aug 24;25(9):104998. doi: 10.1016/j.isci.2022.104998. eCollection 2022 Sep 16.
Foxp3 regulatory T cells (Tregs) are critical mediators of peripheral tolerance and immune homeostasis and exert tissue-specific functions. In many nonlymphoid tissues, Tregs show enriched expression of the IL-33 receptor ST2. Through comprehensive profiling of murine ST2 and ST2 Tregs, we found that Treg transcriptomes and phenotypes formed a hierarchical relationship across tissues. Only a small core signature distinguished ST2 Tregs from ST2 Tregs across all tissues, and differences in transcriptional profiles were predominantly tissue-specific. We also identified unique, highly proliferative, circulating ST2 Tregs with high migratory potential. In adoptive transfers, both ST2 and ST2 Tregs seeded various host tissues and demonstrated plasticity in ST2 expression. Furthermore, Tregs from donor lungs were differentially recovered from host nonlymphoid tissues in an IL-33-dependent manner. In summary, our work identified tissue residency rather than ST2 expression as a primary driver of tissue Treg identity and highlights the unique, tissue-specific adaption of ST2 Tregs.
叉头框蛋白3调节性T细胞（Tregs）是外周耐受和免疫稳态的关键介质，并发挥组织特异性功能。在许多非淋巴组织中，Tregs表现出白细胞介素-33受体ST2的富集表达。通过对小鼠ST2和ST2 Tregs进行全面分析，我们发现Treg转录组和表型在不同组织间形成了层次关系。在所有组织中，只有一个小的核心特征区分了ST2 Tregs和非ST2 Tregs，转录谱的差异主要是组织特异性的。我们还鉴定出具有高迁移潜力的独特、高度增殖的循环ST2 Tregs。在过继转移中，ST2和非ST2 Tregs都定植于各种宿主组织，并在ST2表达上表现出可塑性。此外，来自供体肺的Tregs以白细胞介素-33依赖的方式从宿主非淋巴组织中被不同程度地回收。总之，我们的研究确定组织驻留而非ST2表达是组织Treg特性的主要驱动因素，并突出了ST2 Tregs独特的、组织特异性的适应性。
